Multiple Sclerosis

Anchor the workup to a clinically compatible central nervous system demyelinating syndrome, then use clinical and paraclinical evidence to demonstrate dissemination in space and time while excluding a better explanation. The 2024 McDonald revisions incorporate MRI and CSF biomarkers within a unified diagnostic approach, but the diagnostic framework still requires integration with the clinical presentation and competing diagnoses. The Lancet+1The LancetDiagnosis of multiple sclerosis: 2024 revisions ...ScienceDirectConsensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelines

Obtain MRI to identify lesions in the brain and spinal cord that support MS. When the initial MRI and clinical history do not establish dissemination, use interval MRI and CSF analysis to resolve uncertainty rather than assigning MS from nonspecific symptoms or a single lesion pattern. MRI, lumbar puncture, OCT, and visual evoked potentials can each provide supportive evidence, but none substitutes for exclusion of clinically plausible alternatives. The Lancet+2The LancetDiagnosis of multiple sclerosis: 2024 revisions ...ScienceDirectConsensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelinesWHOMultiple sclerosis

Interpret CSF oligoclonal IgG bands or an elevated IgG index as intrathecal immune activity that can support MS in the appropriate clinical-MRI context. Do not treat oligoclonal bands as disease-specific: they can occur outside MS and should be weighed against the overall CSF profile, MRI phenotype, and clinical red flags. The Lancet+1The LancetApplying the 2017 McDonald diagnostic criteria for multiple ...The LancetCSF testing for multiple sclerosis

Before corticosteroids, determine whether new neurologic worsening is better explained by infection or another reversible trigger. In pregnancy-specific guidance, urinary tract infection is explicitly identified as an infection to exclude before treating a disabling relapse; the same diagnostic discipline avoids treating infection-associated symptom recrudescence as active inflammatory relapse. BMJ+1BMJUK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines | Practical NeurologyBMJUK consensus on pregnancy in multiple sclerosis

For a disabling relapse, administer intravenous methylprednisolone at the recommended MS relapse dose. During pregnancy, this treatment is recommended regardless of trimester after infection has been excluded, and it can also be given while breastfeeding. BMJ+1BMJUK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines | Practical NeurologyBMJUK consensus on pregnancy in multiple sclerosis

For a very severe relapse that fails to respond to corticosteroids, consider plasma exchange. This escalation is reserved for corticosteroid-refractory, severe deficits rather than routine relapse care. BMJ+1BMJUK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines | Practical NeurologyBMJUK consensus on pregnancy in multiple sclerosis

Initiate disease-modifying therapy as early as possible in MS to reduce relapse frequency and severity and to slow disease progression. In relapsing disease, current treatment strategy emphasizes early and complete suppression of inflammatory activity, reflected by relapses and new MRI activity. ScienceDirect+1ScienceDirectUpdate in multiple sclerosisWHOMultiple sclerosis

For relapsing MS, choose between escalation from lower-risk therapies and early use of higher-efficacy therapy according to disease activity, prognostic concern, prior treatment response, comorbidity, and the patient’s tolerance for serious adverse effects and monitoring. More effective therapies can carry more serious safety liabilities, so treatment selection is a benefit-risk decision rather than a uniform sequence. BMJ+1BMJDisease modifying therapies for relapsing multiple sclerosisWolters KluwerHighly Aggressive Multiple Sclerosis - Continuum

Ocrelizumab is a potent CD20-directed B-cell-depleting immunotherapy used in relapsing MS and primary progressive MS. It is used as a second-line option when first-line treatment is insufficient and may be used first line in highly active disease; it remains the approved disease-modifying option for primary progressive MS. NatureNatureReal-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials | Scientific Reports

Do not equate relapse control with absence of disability progression. Relapse-associated worsening and progression independent of relapse activity both contribute to disability accumulation, including among patients treated with ocrelizumab; therefore, monitor disability trajectory as well as overt relapses and MRI activity. Nature+1NatureReal-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials | Scientific ReportsNatureEstimating individual treatment effect on disability progression in multiple sclerosis using deep learning | Nature Communications

Discuss pregnancy intent before starting or changing a disease-modifying therapy in every patient with childbearing potential. Pregnancy should not automatically delay initiation of DMT, because delaying treatment or routinely stopping treatment before pregnancy or immediately after conception is associated with increased relapse risk during pregnancy and may adversely affect long-term disability. BMJ+1BMJUK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines | Practical NeurologyBMJUK consensus on pregnancy in multiple sclerosis

Relapse frequency decreases naturally during pregnancy, but patients with very active disease may require continued treatment through pregnancy. Individualize this decision against fetal and maternal treatment considerations rather than applying a universal stop rule. BMJ+1BMJUK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines | Practical NeurologyBMJUK consensus on pregnancy in multiple sclerosis

MRI is not contraindicated during pregnancy, but avoid gadolinium contrast when possible. If a disabling relapse occurs, offer intravenous methylprednisolone after excluding infection; plasma exchange is an option for a very severe steroid-refractory relapse. BMJ+1BMJUK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines | Practical NeurologyBMJUK consensus on pregnancy in multiple sclerosis

At each longitudinal visit, separately assess relapse history, treatment-associated complications, disability progression, fatigue, spasticity, mood symptoms, urinary dysfunction, and sexual dysfunction. Symptomatic medications may address these manifestations but do not change the underlying disease course, so a symptomatic response should not be interpreted as evidence of inflammatory control. WHOWHOMultiple sclerosis

Refer for rehabilitation when gait, upper-extremity function, endurance, or spasticity limits activity. Rehabilitation specialists can improve functioning and quality of life and reduce stiffness and spasms, providing a parallel intervention when immunotherapy cannot reverse established disability. WHOWHOMultiple sclerosis

When disability worsens without a clear relapse, evaluate for progression independent of relapse activity rather than repeatedly administering relapse therapy. Progressive biology is increasingly recognized in relapsing disease and predominates in progressive MS, while the absence of analogous MRI endpoints limits direct measurement of this process. Nature+1NatureReal-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials | Scientific ReportsNatureEstimating individual treatment effect on disability progression in multiple sclerosis using deep learning | Nature Communications